PK/PD modeling of flunixin meglumine in a kaolin‐induced inflammation model in piglets

Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty‐two piglets (6–8 days old) were randomized to receive placebo saline (n = 11, group CONTROL) or flunixin meglumine intravenously at 2.2 (n = 11, group MEDIUM) or 4.4 (n = 10, group HIGH) mg/kg, 10 hr after subcutaneous injection of kaolin in the left metacarpal area. A hand‐held algometer was used to determine each piglet’s mechanical nociceptive threshold (MNT) from both front feet up to 50 hr after treatment (cut‐off value of 24.5 newton). Serial venous blood samples were obtained to quantify flunixin in plasma using LC‐MS/MS. A PKPD model describing the effect of flunixin on the mechanical nociceptive threshold was obtained based on an inhibitory indirect response model. A two‐compartmental PK model was used. A significant effect of flunixin was observed for both doses compared to control group, with 4.4 mg/kg showing the most relevant (6–10 newton) and long‐lasting effect (34 hr). The median IC50 was 6.78 and 2.63 mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6 mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin‐induced inflammatory hyperalgesia in piglets.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.     

Effect of a 1800 MHz electromagnetic field emitted during embryogenesis on chick development and hatchability

The level of artificial electromagnetic field (EMF) has steadily increased with the development of human civilization. The developing chicken embryo has been considered a good model to study the effects of EMF on living organisms. The aim of the study was to determine the effect of a 1800 MHz electromagnetic field during embryogenesis on the frequency of chick embryo malformations, morphometric parameters of the heart and liver and concentration of corticosterone in blood plasma, lipid and glycogen content in the liver of newly hatched chicks. A 1800 MHz EMF was found to shorten the duration of embryogenesis (earlier pipping and hatching of chicks) while having no effect on the quantity and quality of chicks and on increasing the incidence of embryo malformations. Exposure of chick embryos to EMF caused decreases in relative heart weight and right ventricle wall thickness. The pipping and hatching of chicks can be accelerated by stressful impact of EMF, which is confirmed by a significant increase in plasma corticosterone concentrations and decrease in fat and glycogen in the liver of chicks exposed during embryogenesis on the electromagnetic field with a frequency of 1800 MHz.     

Macro‐anatomical and morphometric studies of the hindlimb of grasscutter (Thryonomys swinderianus,Temminck‐1827)

The hindlimb of the grasscutter (Thryonomys swinderianus, Temminck‐1827) was studied using 12 adult (≥6 months) rats of either sex with the mean weights of 1.42 ± 0.20 kg and 0.82 ± 0.13 kg for buck (n = 6) and doe (n = 6), respectively (p < .05). Characteristics of the bones were studied by gross observation after their preparation. Measurements of different segments of the hindlimb were also taken, giving a total average length of 31.80 cm. Correlation coefficients between length of bone and weight of rats were positive (p < .05) in bucks for all bone segments, except the pes (p > .05), whereas those in does were all non‐significant (p > .05), with significant sexual dimorphism in the relationships. The average total number of bones in the hindlimb was 92, with no apparent sexual dimorphism. The bones of the hindlimb revealed important differences and similarities in morphology with those of other rodents. The Os coxae presented a relatively large obturator foramen, formed by the ramus of the ischium and shaft of the pubis. The femur had a body and two extremities with a prominent head, well‐defined neck and trochanter. The fibula, a slender bone with triangular‐shaped proximal extremity, ran down the length of tibia with proximal attachment (via cartilage) and distal fusion, leaving an extensive interosseus space. The pes revealed eight tarsals and four metatarsals; each of the metatarsals showed three phalanges.     

Categorization of the pelvic limb standing posture in nine breeds of dogs

The objective of the study was to categorize objectively nine breeds of healthy dogs according to pelvic limb standing posture. A total of 135 dogs from different breeds were used and the standing angles of the hip, stifle, and tarsal joints, together with the percentages of the greater trochanter, patella and tuber calcanei heights, with respect to crista iliaca height, were used as discriminant variables for the categorization of pelvic limb posture. All included breeds were allocated to three groups of the standing pelvic limb posture. The best discriminant variables between the three groups were the percentage of patellar height, and the standing angles of the stifle and tarsal joints. German shepherds, Anatolian shepherds, golden retrievers, Rottweilers, Belgian Malinois and Dobermann pinschers were well separated between 89% and 100% success rate for the categorization. The minimal success rate was determined in Berner sennenhunds as the ratio of 75%. It was also determined that Dobermann pinschers had the straightest pelvic limbs, while German shepherds had the most angulated pelvic limbs. Further studies are required to document the impact of postural differences in active and passive structure diseases of the locomotor system of the pelvic limb among dog breeds.     

Evaluation of three popular diets fed to pet sugar gliders (Petaurus breviceps): Intake,digestion and nutrient balance

Three diets fed to 12 pair‐housed sugar gliders, Petaurus breviceps, were evaluated through 5‐day intake and digestion trials following 10‐day transitions. Diets 1 and 2 comprised liquid formula mixes with added vegetables and fruit, and Diet 3 comprised extruded pellets and a liquid formula. Diets eaten contained 16 —19% crude protein, 3%–15% crude fat, 10%–11% neutral detergent fibre, 4%–20% starch and 8%–49% sugar (dry basis). Calculated individual dry matter intakes (DMI) ranged from 3.9 to 5.1 g/day, representing 58.2–78.4 kJ/day. DMI was greater for Diet 2 (7.2% BW) vs. Diet 1 (5.6; p = .006) and Diet 3 (4.2% BW; p = .003). Although these differences were no longer detectable on a MBW basis, animals were shown to have gained BW (+14.2 g; p = .03) on Diet 2. In addition to nutrient composition differing widely among diets, DM digestibility (DMD) was higher in Diet 1 (91.2%) compared to Diet 2 (87.3%; p = .03), but DMD for Diet 3 (88.9%) did not differ from other diets. Gliders demonstrated ability to digest a variety of energy substrates, including simple sugars (96%–99%), fats (81%–96%) and starches (79%–98%), as well as substantial insoluble dietary fibre (58%–75%), with significant difference among diets demonstrated for some nutrients. Animals displayed selective feeding behaviours, rejecting insoluble fibre in produce and preferring the lipid‐coated exterior of pellets. The diets used appeared to be balanced with respect to energy, protein and macromineral content, but may predispose to iron excess, other mineral imbalances (especially Ca deficiency) and obesity—clinical health issues described for pet gliders. Future focus on concentrations, types and utilization of dietary fibre in natural and captive diets, vitamin D metabolism and trace mineral interactions in sugar gliders would assist diet optimization for this highly gummivorous species.